Greater cumulative benefits from ixekizumab versus ustekinumab treatment over 52 weeks for patients with moderate-to-severe psoriasis in a randomized, double-blinded phase 3b clinical trial

<b>Background</b>: Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-17A, has shown superiority to ustekinumab (UST) and etanercept in skin clearance from randomized clinical trials in patients with moderate-to-severe psoriasis. <b>Objective:</b> To compare cumulative benefits of IXE versus UST over 52 weeks of treatment. <b>Methods:</b> Cumulative clinical benefit of IXE and UST was assessed by evaluating the area under the curve (AUC) for responders of Psoriasis Area and Severity Index (PASI), itch numeric rating scale (Itch NRS), and Dermatology Life Quality Index (DLQI) outcomes over 52 weeks using data from IXORA-S trial comparing IXE (<i>N</i> = 136) and UST (<i>N</i> = 166). Normalized cumulative benefit was calculated to obtain the percentage of the maximum AUC for each outcome measure. Missing values were imputed using non-responder imputation. <b>Results:</b> Significantly greater cumulative benefits were obtained for IXE compared with UST. Normalized cumulative benefit with IXE versus UST for PASI 75/90/100, Itch NRS (0), and DLQI (0,1) were 83.1% and 67.6%; 68.9% and 46.5%; 41.1% and 23.4%; 40.4% and 30.9%; and 62.2% and 46.6%, respectively. Cumulative clinical benefit ratios for IXE:UST were 1.23 for PASI 75, 1.48 for PASI 90, and 1.76 for PASI 100, indicating an increase in the cumulative clinical benefit for IXE versus UST as the clearance levels increased. <b>Conclusions:</b> IXE showed greater cumulative clinical benefit than UST.

<b>背景</b>：依奇珠单抗（Ixekizumab, IXE）是一种高亲和力的选择性靶向白细胞介素-17A（interleukin-17A）的单克隆抗体，在针对中度至重度银屑病患者的随机临床试验中，其皮肤清除效果优于乌司奴单抗（ustekinumab, UST）与依那西普（etanercept）。<b>研究目的</b>：比较依奇珠单抗与乌司奴单抗在52周治疗周期内的累积临床获益情况。<b>研究方法</b>：本研究采用IXORA-S临床试验的数据，对比依奇珠单抗组（<i>N</i> = 136）与乌司奴单抗组（<i>N</i> = 166）的患者数据，通过计算52周内银屑病面积和严重程度指数（Psoriasis Area and Severity Index, PASI）、瘙痒数字评分量表（Itch Numeric Rating Scale, Itch NRS）以及皮肤病学生活质量指数（Dermatology Life Quality Index, DLQI）应答者的曲线下面积（area under the curve, AUC），评估两组的累积临床获益。通过归一化计算得到各结局指标对应的最大曲线下面积百分比。缺失值采用无应答者插补法进行补全。<b>研究结果</b>：相较于乌司奴单抗，依奇珠单抗的累积临床获益显著更高。依奇珠单抗与乌司奴单抗在PASI 75/90/100、瘙痒NRS（0分）以及DLQI（0分、1分）的归一化累积获益分别为83.1%与67.6%、68.9%与46.5%、41.1%与23.4%、40.4%与30.9%以及62.2%与46.6%。依奇珠单抗与乌司奴单抗的累积临床获益比值为：PASI 75的1.23、PASI 90的1.48以及PASI 100的1.76，提示随着皮肤清除等级提升，依奇珠单抗相较于乌司奴单抗的累积临床获益进一步增加。<b>结论</b>：依奇珠单抗的累积临床获益优于乌司奴单抗。